Supplemental Figures

Supplemental Figure 1: ONC201 doses versus (A) Cmax and (B) AUC determined after the

first dose of ONC201. * Anticipated dose proportionality line based on mean for 625 mg dose

group.

Supplemental Figure 2: Covariant analyses of pharmacokinetic parameters. Individual CL/F

versus ONC201 dose (A), sex (B), age (C), weight (D), BSA (E). Individual Vz/F versus patient

weight (F) or BSA (G). Individual dose-normalized Cmax versus patient weight (H), Individual

dose-normalized AUC versus patient weight (I) and Individual dose-normalized CL/F versus

ONC201 dose (J).

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Supplemental Figure 3: Caspase-cleaved versus total cytokeratin 18 at baseline and 21

days following the first dose of 625mg ONC201 in (A) an ovarian cancer patient (disease

progression within 3 weeks) and (B) a prostate cancer patient (stable disease > 20 weeks).

Supplemental Figure 4: Serum TRAIL ELISA assay following the first dose of ONC201. (A)

TRAIL expression for patients in dose-escalation cohorts (125-500mg). (B) Serum TRAIL

expression for patients at top dose-level cohort (625mg). Each point is an average of 2

independent plasma measurements. Error bars indicate standard deviation.

2

Supplemental Figure 5: Serum prolactin induction. Baseline and maximum post-treatment

serum prolactin levels in dose-expansion cohort of patients.

Supplemental Figure 6: Serum prolactin induction versus ONC201 exposure. Peak prolactin

induction versus (A) ONC201 dose, and the PK parameters (B) Cmax and (C) AUC for

patients in dose-escalation cohorts.

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Supplemental Tables

Supplemental Table 1. Patient demographics with ONC201 administered every three

weeks in dose escalation phase and in the expansion phase with ONC201 RP2D. *

Indicates patient remains on study.

Pat # Tumor TypeAge Se

xECO

GWeigh

tONC20

1(years

) (Kg) (mg)

Dose escalation phase

1 NSCLC 80 F 1 47.3 125

2 Appendiceal adenocarcinoma 47 M 0 77.8 250

3 Uterine cancer 72 F 1 48 3754 Renal cancer 62 M 1 123 5005 Breast cancer 55 F 1 87 625

6 Prostate adenocarcinoma 69 M 0 92.4 625

7 Small cell lung cancer 70 M 1 55 625

8 Colon adenocarcinoma 71 M 0 73.5 625

9 Spindle cell sarcoma 74 F 1 95.2 625

10 Ovarian 68 F 1 61 625Expansion phase

11 Uterine cancer 67 F 0 72.7 62512 Uterine cancer 56 F 0 47.7 62513 Ovarian cancer 64 F 1 49.3 625

14 Gall bladder cancer 75 F 0 60.6 625

15Desmoplastic

small round cell tumor

26 M 1 49.3 625

16 Colon cancer 48 M 1 84.5 625

17 Prostate adenocarcinoma 69 M 1 82.2 625

18 Ovarian cancer 59 F 1 62.7 625

4

19 Prostate adenocarcinoma 62 M 1 118.2 625

20 Uterine cancer 60 F 1 82.7 62521 Lung sarcoma 55 M 1 116.3 62522 Ovarian cancer 57 F 1 51.2 625

23 Cholangiosarcoma 50 F 1 76.8 625

24 Prostate cancer 90 M 1 42.7 62525 Uterine cancer 60 F 1 91.2 625

26 Myxoid liposarcoma 48 F 1 69.5 625

27 Prostate cancer 72 M 0 75.5 62528 Prostate cancer 65 M 1 82.6 625

Median 64 74.5

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Supplemental Table 2: Adverse events occurring on study that were not attributed to

ONC201.

Attribution

Unrelated   Unlikely

Grade 1

Grade 2

Grade 3

Grade 4

Grade 5  

Grade 1

Grade 2

Grade 3

Grade 4

Grade 5

6

Gastrointestinal disorders 36 8 9 0 0   9 3 2 0 0

Nervous system disorders 12 0 0 0 0   2 0 0 0 0

General disorders and administration

site conditions 18 7 0 0 1   7 0 1 0 0

Blood and lymphatic system disorders 16 5 1 0 0   3 0 1 0 0

Metabolism and nutrition disorders 51 14 6 0 0   9 6 1 0 0

Psychiatric disorders 19 0 0 0 0   0 0 0 0 0

Vascular disorders 8 17 4 0 0   0 1 0 0 0

Musculoskeletal and connective tissue

disorders 6 3 4 0 0   1 1 0 0 0

Investigations 54 15 8 0 0   18 2 7 0 0

Respiratory, thoracic and mediastinal

disorders 9 6 1 0 0   1 0 0 0 0

Infections and infestations 0 0 2 0 0   0 0 0 0 0

Skin and subcutaneous tissue

disorders 8 2 0 0 0   0 0 0 0 0

Renal and urinary disorders 13 8 2 0 0   2 1 0 0 0

Endocrine disorders 1 0 0 0 0   0 0 0 0 0

Cardiac disorders 2 0 2 2 0   1 1 0 0 0

Injury, poisoning and procedural

complications 1 0 0 0 0   0 0 0 0 0

Eye disorders 1 0 0 0 0   0 0 0 0 0

Reproductive system and breast disorders 0 0 1 0 0   0 0 0 0 0

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Supplemental Table 3: Individual ONC201 pharmacokinetic parameters for patients in the

dose escalation phase.

Supplemental Table 4: Select characteristics of patients in the dose escalation phase.

BSA, m2

Mean + SD 1.86 + 0.33

(Min – Max) (1.38 – 2.42)

Serum Creatinine, mg/dL

Mean + SD 0.9 + 0.2

(Min – Max) (0.5 – 1.1)

Creatinine Clearance (CLCR), mL/min

Mean + SD 93.2 + 49.5

(Min – Max) (30.4 – 183.6)

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Supplemental Table 5. Clinical responses and pharmacodynamic in the dose escalation

phase. Abbreviations: MR-mixed response, SD – stable disease, PD – Progressive disease.

Tumor type in vitro sensitivity categorization is described in the methods section.

Pat # Tumor Type

ONC201 Best Overall

Response

Time on Treatment

(weeks)

M30 Induction

(>50%)Strength No. of doses(mg)

1 NSCLC 125 4 SD 12 No

2 Appendiceal cancer 250 4 SD 12 No

3 Uterine cancer 375 2 MR 6 Yes

4 Renal cancer 500 2 PD 6 No

5 Breast cancer 625 2 PD 6 Yes

6 Prostate adenocarcinoma 625 9 SD 27 Yes

7 Small cell lung cancer 625 2 PD 6 Yes

8 Colon adenocarcinoma 625 4 SD 12 Yes

9 Spindle cell sarcoma 625 2 PD 6 No

10 Ovarian cancer 625 1 PD 3 No

11 Uterine cancer 125 6 SD 18 Yes

12 Uterine cancer 250 14 SD 42 No

13 Ovarian cancer 375 2 PD 6 No

14 Gall bladder cancer 500 4 SD 12 Yes

15Desmoplastic

small round cell tumor

625 2 PD 6 No

16 Colon cancer 625 2 PD 6 Yes

17 Prostate adenocarcinoma 625 4 SD 12 Yes

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18 Ovarian cancer 625 2 PD 6 Yes

19 Prostate adenocarcinoma 625 6 SD 18 No

20 Uterine cancer 625 2 PD 6 Yes

21 Lung sarcoma 625 2 PD 6 No

22 Ovarian cancer 625 1 PD 3 Yes

23 Cholangiosarcoma 625 2 PD 6 No

24 Prostate cancer 625 4 SD 12 No

25 Uterine cancer 625 3 SD 9 No

26 Myxoid liposarcoma 625 2 PD 6 No

27 Prostate cancer 625 2 PD 6 No

28 Prostate cancer 625 1 PD 3 No

Mean 3.3 10.0

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